Category Archives: Obesity

Cannabidiol partially rescues behavioral, neuroinflammatory and endocannabinoid dysfunctions stemming from maternal obesity in the adult offspring

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“Maternal obesity is known to increase the risk of psychiatric disorders, such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While preventive measures are well-documented, practical approaches for addressing the damages once they are already established are limited.

We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on neuroinflammation and peripheral metabolic disturbances during adolescence, however, it is known that both factors tend to vary throughout life. Therefore, here we investigated the potential of CBD to mitigate these alterations in the adult offspring of obese dams.

Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) for 3 weeks from the 70th day of life. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and endocannabinoid markers were evaluated in the hypothalamus, prefrontal cortex (PFC) and hippocampus, as well as the biochemical profile in the plasma.

CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, restoring exacerbated astrocytic and microglial markers in the hypothalamus, PFC and hippocampus of the offspring, as well as endocannabinoid levels in the PFC, with notable sex differences. Additionally, CBD attenuated plasma glucose and lipopolysaccharides (LPS) concentrations in females.

These findings underscore the persistent influence of maternal obesity on the offspring’s health, encompassing metabolic irregularities and behavioral impairments, as well as the role of the endocannabinoid system in mediating these outcomes across the lifespan.”

https://pubmed.ncbi.nlm.nih.gov/39447736/

“Treatment with cannabidiol rescues anxiety and social disturbances in the offspring.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390824003654?via%3Dihub


Maternal obesity induces sex-specific changes in the endocannabinoid system of the hypothalamus and dorsal hippocampus of offspring associated with anxiety-like behavior in adolescent female rats

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“Maternal obesity during perinatal period increases the risk of metabolic and behavioral deleterious outcomes in the offspring, since it is critical for brain development, maturation, and reorganization. These processes are highly modulated by the endocannabinoid system (ECS), which comprises the main lipid ligands anandamide and 2-arachidonoylglycerol, cannabinoid receptors 1 and 2 (CB1R and CB2R), and several metabolizing enzymes.

The ECS is overactivated in obesity and it contributes to the physiological activity of the hypothalamus-pituitary-adrenal (HPA) axis, promoting stress relief. We have previously demonstrated that maternal high-fat diet during gestation and lactation programmed the food preference for fat in adolescent male offspring and adult male and female offspring.

In the present study, we hypothesized that maternal diet-induced obesity would induce sex-specific changes of the ECS in the hypothalamus and dorsal hippocampus of rat offspring associated with dysregulation of the HPA axis and stress-related behavior in adolescence. Rat dams were fed a control (C) or an obesogenic high-fat high-sugar diet (OD) for nine weeks prior to mating and throughout gestation and lactation. Maternal obesity differentially altered the CB1R in the hypothalamus of neonate offspring, with significant increase in male but not in female pups, associated with decreased CB2R prior to obesity development. In adolescence, maternal obesity induced anxiety-like behavior only in adolescent females which was associated with increased content of CB1R in the dorsal hippocampus.

Our findings suggest that the early origins of anxiety disorders induced by maternal exposome is associated with dysregulation of the brain ECS, with females being more susceptible.”

https://pubmed.ncbi.nlm.nih.gov/39362071/

“The prevalence of obesity has reached pandemic proportions worldwide, and it is important to better understand the impact of maternal obesity on offspring metabolic health and susceptibility to neurodevelopmental and neuropsychiatric disorders such as anxiety and depression. In the present study, we used a rat model of maternal diet-induced obesity to explore these interactions. The main findings of this study were that maternal obesogenic diet elicited sex-specific molecular changes on the ECS.”

https://www.sciencedirect.com/science/article/abs/pii/S0018506X24001739?via%3Dihub

The endocannabinoid system in appetite regulation and treatment of obesity

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“The endocannabinoid system (ECS) is a complex cell-signaling system that is responsible for maintaining homeostasis by modulating various regulatory reactions in response to internal and environmental changes. The influence of ECS on appetite regulation has been a subject of much recent research, however, the full extent of its impact remains unknown.

Current evidence links human obesity to ECS activation, increased endocannabinoid levels in both central and peripheral tissues, along with cannabinoid receptor type 1 (CBR1) up-regulation. These findings imply the potential pharmacological use of the ECS in the treatment of obesity.

Here, we present various pathophysiological processes in obesity involving the ECS, highlighting different pharmacological options for modulating endocannabinoid activity to treat obesity. However, the potential of those pharmacological possibilities remains under investigation and requires further research.”

https://pubmed.ncbi.nlm.nih.gov/39292202/

The effects of Cannabis sativa and cannabinoids on the inhibition of pancreatic lipase – An enzyme involved in obesity

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“Introduction: Obesity is a chronic noncommunicable disease characterized by excessive body fat that can have negative health consequences. Obesity is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. It is characterized by a discrepancy between caloric intake and expenditure. Obesity increases the risk of acquiring major chronic diseases, including heart disease, stroke, cancer, and Type 2 diabetes mellitus (T2DM). Currently, the inhibition of pancreatic lipases (PL) is a promising pharmacological therapy for obesity and weight management. In this study, the inhibition of pancreatic lipase by Cannabis sativa (C. sativa) plant extract and cannabinoids was investigated.

Methods: The inhibitory effect was assessed using p-nitrophenyl butyrate (pNPB), and the results were obtained by calculating the percentage relative activity and assessed using one-way analysis of variance (ANOVA). Kinetic studies and spectroscopy techniques were used to evaluate the mode of inhibition. Diet-induced; and diabetic rat models were studied to evaluate the direct effects of C. sativa extract on PL activity.

Results: Kinetic analyses showed that the plant extracts inhibited pancreatic lipase, with tetrahydrocannabinol (THC) and cannabinol (CBN) being the potential cause of the inhibition noted for the C. sativa plant extract. CBN and THC inhibited the pancreatic lipase activity in a competitive manner, with the lowest residual enzyme activity of 52 % observed at a 10 μg/mL concentration of CBN and 39 % inhibition at a 25 μg/mL concentration of THC. Circular dichroism (CD) spectroscopy revealed that the inhibitors caused a change in the enzyme’s secondary structure. At low concentrations, THC showed potential for synergistic inhibition with orlistat. C.sativa treatment in an in vivo rat model confirmed its inhibitory effects on pancreatic lipase activity.

Conclusion: The findings in this study provided insight into the use of cannabinoids as pancreatic lipase inhibitors and the possibility of using these compounds to develop new pharmacological treatments for obesity.”

https://pubmed.ncbi.nlm.nih.gov/39232382/

https://www.sciencedirect.com/science/article/pii/S0753332224012423?via%3Dihub

A National Survey of Marijuana Use Among U.S. Adults According to Obesity Status, 2016-2022

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“Background and Objective: Research has linked marijuana use with lower body mass index (BMI). The current study explores the correlation between marijuana use on BMI in the general U.S. population. It reports the prevalence of marijuana in adults in relation to BMI, overall and across the levels of important variables. 

Materials and Methods: This study used a probability sample of U.S. adults 18 years of age and older from the 2016 through 2022 Behavioral Risk Factor Surveillance System, a telephone-administered survey. The survey collects data from a representative sample regarding health-related risk behaviors, chronic health conditions, and use of preventive services. The primary outcome variables are current (at least once in the last 30 days) and daily (at least 20 of the last 30 days) marijuana use. 

Results: The study sample consists of 735,921 participants in the surveys that completed the optional module on marijuana use. Prevalence of marijuana use in adults doubled during the study period (7.48% to 14.91%). The increase directly corresponds with a shift toward legalization of medical and recreational marijuana. On average, the prevalence of use is 9% higher when medical marijuana is legal and 81% higher when recreational marijuana is legal (vs. not legal). For obese individuals, prevalence of current marijuana use is 35% lower than for nonobese individuals on average. Lower prevalence of marijuana use in obese individuals is consistently observed across the levels of certain demographic variables, employment status, tobacco smoking history, marijuana legalization status, and certain medical conditions (asthma, arthritis, and depression). In 2022, the adjusted odds of current or daily marijuana use are significantly lower and similar among obese (vs. non-obese) (0.68, 0.69, respectively), such that reduced obesity does not require daily use. Similarly, the adjusted odds of current marijuana use decrease in similar fashion to daily marijuana use with higher BMI weight classification. 

Conclusion: Marijuana use is correlated with lower BMI. As legalization and prevalence of the drug in the U.S. increases, the prevalence of obesity may decline. However, clinicians should view this outcome along with the known health risks associated with marijuana use.”

https://pubmed.ncbi.nlm.nih.gov/39158998/

https://www.liebertpub.com/doi/10.1089/can.2024.0069

Cannabidiol improves maternal obesity-induced behavioral, neuroinflammatory and neurochemical dysfunctions in the juvenile offspring

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“Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established.

We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams.

Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus.

CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes.

Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/38608740/

https://www.sciencedirect.com/science/article/abs/pii/S0889159124003556?via%3Dihub

The Effect of Oil-Based Cannabis Extracts on Metabolic Parameters and Microbiota Composition of Mice Fed a Standard and a High-Fat Diet

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“The prevalence of obesity and obesity-related pathologies is lower in frequent cannabis users compared to non-users. It is well established that the endocannabinoid system has an important role in the development of obesity.

We recently demonstrated that prolonged oral consumption of purified Δ-9 Tetrahydrocannabinol (THC), but not of cannabidiol (CBD), ameliorates diet-induced obesity and improves obesity-related metabolic complications in a high-fat diet mouse model. However, the effect of commercially available medical cannabis oils that contain numerous additional active molecules has not been examined.

We tested herein the effects of THC- and CBD-enriched medical cannabis oils on obesity parameters and the gut microbiota composition of C57BL/6 male mice fed with either a high-fat or standard diet. We also assessed the levels of prominent endocannabinoids and endocannabinoid-like lipid mediators in the liver.

THC-enriched extract prevented weight gain by a high-fat diet and attenuated diet-induced liver steatosis concomitantly with reduced levels of the lipid mediators palmitoyl ethanolamide (PEA) and docosahexaenoyl ethanolamide (DHEA) in the liver. In contrast, CBD-enriched extract had no effect on weight gain, but, on the contrary, it even exacerbated liver steatosis. An analysis of the gut microbiota revealed that mainly time but not treatment exerted a strong effect on gut microbiota alterations.

From our data, we conclude that THC-enriched cannabis oil where THC is the main constituent exerts the optimal anti-obesity effects.”

https://pubmed.ncbi.nlm.nih.gov/38256146/

https://www.mdpi.com/1422-0067/25/2/1073

How Does CBG Administration Affect Sphingolipid Deposition in the Liver of Insulin-Resistant Rats?

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“Background: Cannabigerol (CBG), a non-psychotropic phytocannabinoid found in Cannabis sativa plants, has been the focus of recent studies due to its potential therapeutic properties. We proposed that by focusing on sphingolipid metabolism, which plays a critical role in insulin signaling and the development of insulin resistance, CBG may provide a novel therapeutic approach for metabolic disorders, particularly insulin resistance.

Methods: In a rat model of insulin resistance induced by a high-fat, high-sucrose diet (HFHS), we aimed to elucidate the effect of intragastrically administered CBG on hepatic sphingolipid deposition and metabolism. Moreover, we also elucidated the expression of sphingolipid transporters and changes in the sphingolipid concentration in the plasma.

Results: The results, surprisingly, showed a lack of changes in de novo ceramide synthesis pathway enzymes and significant enhancement in the expression of enzymes involved in ceramide catabolism, which was confirmed by changes in hepatic sphingomyelin, sphinganine, sphingosine-1-phosphate, and sphinganine-1-phosphate concentrations.

Conclusions: The results suggest that CBG treatment may modulate sphingolipid metabolism in the liver and plasma, potentially protecting the liver against the development of metabolic disorders such as insulin resistance.”

https://pubmed.ncbi.nlm.nih.gov/37892425/

https://www.mdpi.com/2072-6643/15/20/4350

The Effect of Orally Administered Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on Obesity Parameters in Mice

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“Prolonged cannabis users show a lower prevalence of obesity and associated comorbidities. In rodent models, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) from the plant Cannabis sativa L. have shown anti-obesity properties, suggesting a link between the endocannabinoid system (ECS) and obesity. However, the oral administration route has rarely been studied in this context. The aim of this study was to investigate the effect of prolonged oral administration of pure THC and CBD on obesity-related parameters and peripheral endocannabinoids. C57BL/6 male mice were fed with either a high-fat or standard diet and then received oral treatment in ramping doses, namely 10 mg/kg of THC or CBD for 5 weeks followed by 30 mg/kg for an additional 5 weeks. Mice treated with THC had attenuated weight gain and improved glucose tolerance, followed by improvement in steatosis markers and decreased hypertrophic cells in adipose epididymal tissue. Mice treated with CBD had improved glucose tolerance and increased markers of lipid metabolism in adipose and liver tissues, but in contrast to THC, CBD had no effect on weight gain and steatosis markers. CBD exclusively decreased the level of the endocannabinoid 2-arachidonoylglycerol in the liver. These data suggest that the prolonged oral consumption of THC, but not of CBD, ameliorates diet-induced obesity and metabolic parameters, possibly through a mechanism of adipose tissue adaptation.”

https://pubmed.ncbi.nlm.nih.gov/37762099/

“In conclusion, the present findings provide evidence for the ability of THC to improve obesity-related metabolic complications when administered orally in ramping doses. The limited effect of CBD demonstrated in our study suggests that the low prevalence of obesity and metabolic diseases seen in cannabis users is mainly attributed to the presence of THC.”

https://www.mdpi.com/1422-0067/24/18/13797

Therapeutic effect of cannabidiol on myocardial arachidonic acid content in various lipid fractions in a rat model of obesity

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“The study explored the potential protective influence of cannabidiol (CBD) on myocardial inflammation state, with a special focus on arachidonic acid (AA), and oxidative balance in lipid overload conditions.

The 7-week experiment was conducted on male Wistar rats receiving standard or high-fat diet (HFD) with intraperitoneal CBD injections for the last 14 days. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) activities and AA concentration in selected fractions were evaluated by gas-liquid chromatography (GLC). The expression of proteins was determined by Western blot and the concentration of different parameters by ELISA, colorimetric, or multiplex assay kits.

Our results revealed that CBD increased n-3 PUFAs activity in phospholipid and triacylglycerol fractions, and decreased AA content in the HFD group, especially in the phospholipid pool. Simultaneously, CBD decreased the expression of nuclear factor kappa B, cyclooxygenase-1, and -2, resulting in the reduction of prostaglandin E2 and the increment of prostaglandin I2.

CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties.”

https://pubmed.ncbi.nlm.nih.gov/37541613/

https://www.sciencedirect.com/science/article/abs/pii/S1098882323000643?via%3Dihub